High and low responders to novelty: Effects of a catecholamine synthesis inhibitor on novelty-induced changes in behaviour and release of accumbal dopamine

The purpose of the present study was two-fold: (i) to investigate to what e xtent novelty, i.e. a novel cage with slightly larger dimensions than the h ome cage and lacking the floor covering that was originally present, produc ed behavioural effects in high responders to novelty and low responders to novelty that could be correlated with the extracellular amount of accumbal dopamine, using the microdialysis technique, and (ii) to establish the abil ity of the catecholamine synthesis inhibitor a-methyl-p-tyrosine to inhibit the novelty-induced responses in high and low responders. The difference i n the behavioural response to novelty between the high and low responders w as limited to walking, which lasted significantly longer in high responders than in low responders. The novelty-induced increase in extracellular conc entration of accumbal dopamine was significantly greater in high responders than in low responders; moreover, the shape of the growth curves differed between high and low responders. The behavioural changes did not correlate with the neurochemical effects, which outlasted the duration of the novelty -induced behavioural arousal. II is hypothesized that this long-lasting inc rease in accumbal dopamine produces "adaptive changes" that help and/or all ow the animal to incorporate knowledge about the condition that it experien ced. When the nucleus accumbens was perfused with alpha-methyl-p-tyrosine f or a period of 40 min, given at the same time as the transfer of the rat to the novel cage, it reduced the novelty-induced increase in walking in the high responders, but did not alter the novelty induced behaviour of low res ponders. Finally, alpha-methyl-p-tyrosine reduced the novelty-induced incre ase in the release of accumbal dopamine in high responders, but enhanced it in low responders. The present neurochemical data are discussed in view of the outcome of earl ier reported pharmaco-behavioural studies on the neurochemical slate of the nucleus accumbens of non-challenged versus challenged high and low respond ers. It is hypothesized that, in the high responder, exposure to novelty en hances the release of accumbal dopamine from reserpine-resistant, alpha-met hyl-p-tyrosine-sensitive pools that are under the stimulatory control of be ta-adrenergic receptors in the nucleus accumbens, and that, in the low resp onder, exposure to novelty enhances the release of accumbal dopamine from r eserpine-sensitive, alpha-methyl-p-tyrosine-resistant pools that are under the inhibitory control of alpha-adrenergic receptors in the nucleus accumbe ns. (C) 1998 IBRO. Published by Elsevier Science Ltd.